Interventional Fluoroscopy Fluoroscopically-guided radiation procedures can result in high radiation exposure to both the physician and patient. A cohort of physicians who perform interventional radiation procedures, radiologists and a comparison group has been assembled to estimate the risk of dying from cancer especially brain and leukemia. Analyses are in progress. Multiple Primary Systems REB investigators evaluate the risks of multiple cancers following all cancers using the Surveillance Epidemiology and End Results Program cancer registry database including more than 2 million cancer survivors diagnosed from 1973 to 2008. Interesting findings from the 2006 Multiple Primary Monograph have been followed up with individual studies evaluating risk of radiation-related and chemotherapy-related second cancers. Particular studies of interest include of survivors of breast cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, retinoblastoma, and childhood cancers. Pilot Work for Genome-wide Association Study of Second Cancers Following Childhood Cancer The Childhood Cancer Survivor Study is a unique resource and a rare opportunity in which to examine the potential for gene-radiation interaction. Particularly noteworthy are the availability of biospecimens, high quality information on doses of radiation and chemotherapy, and the young age at exposure of the cohort. We are currently evaluating the possibility of performing a genome wide association scan for second cancers within this cohort. Breast and Other Cancers Following X-Rays for Scoliosis A multi-center retrospective cohort study of female scoliosis patients monitored with diagnostic x-rays, found a statistically significant 70% excess in breast cancer mortality compared to the general population. Risk increased significantly with increasing radiation dose to the breast. Death rates from other cancers (lung, cervical, liver) were lower than expected. A similar relationship was observed for breast cancer incidence. Cancer Following Radiotherapy for Benign Gynecologic Disorders Cancer mortality following radiation treatment for benign gynecologic conditions in a cohort of nearly 15,000 women with individual radiation dose data is being updated to evaluate solid tumor and leukemia risk. Childhood Cancer Survivor Study (CCSS) In a cohort of 14,000 5-year survivors of childhood cancer we performed nested case-control studies of second primary cancers of the breast, thyroid gland, Saliva/Buccal Cellsry gland, bone, soft tissue and skin to evaluate the relationship between radiation and chemotherapy and risk of these cancers. A novel finding was that thyroid cancer risk was related to prior treatment with alkylating agents among patients exposed to radiation less than 20 Gy to the thyroid. Cancer Risk in Peptic Ulcer Patients A of cohort of 2000 irradiated peptic ulcer patients is being compared to 2000 non-irradiated peptic ulcer patients to refine the dose-related risk for all cancers and cardiac disease and model the uncertainty in the dose estimates for these outcomes. Proton IMRT Proton and intensity-modulated radiation therapy have the potential to deliver maximal doses to the tumor while minimizing dose to the surrounding tissues which may cause second cancers. An international feasibility study to evaluate the risk of second cancers from this treatment has been initiated. RF Analysis of Hematopoietic Malignancies in Various Radiotherapeutically Irradiated Cohorts Parallel analysis using a variety of mathematical and statistical models of cancer risks associated with ionizing radiation exposure in the Japanese atomic bomb survivors and in therapeutically irradiated groups. Endpoints include all hematologic cancers, specifically leukemia (including chronic lymphocytc leukemia (CLL)), Hodgkins disease, non-Hodgkins lymphoma (NHL), and multiple myeloma. The models take account of cell repopulation and redistribution as a result of internal and external radiation exposure (including brachytherapy), and also factors such as age at exposure and attained age. Radiation Dose-Response and Second Primary Cancers of Stomach, Esophagus, and Pancreas An international study of second primary gastrointestinal (GI stomach cancer, pancreatic cancer, and esophageal cancer) cancers is being conducted among survivors of Hodgkin lymphoma testis cancer, breast and cervical cancer to provide new data on radiation dose and subsequent risk of GI cancer. Findings to date have demonstrated a dose-related increased risk of esophageal cancer following breast cancer. Analyses of GI malignancy risk after HL and testis and cervical cancers are in progress. Risk Factors for Second Cancers in the Cohort Consortium The feasibility of studying second cancers in the NCI Cohort Consortium is being assessed. Second Cancers after Breast Cancer in three Cohorts (Kaiser, Million women study and AARP) The etiology of contralateral breast is probably related to treatment, genetic and lifestyle risk factors. We are exploring the feasibility of studying treatment and modifiable lifestyle risk factors for contralateral breast cancer in three different cohorts. Second Cancers Following Retinoblastoma A cohort of 1,850 Retinoblastoma survivors continues to be monitored for the incidence and mortality of all second primary cancers, primarily of the bone, soft tissue, and melanoma in relation to past radiotherapy and chemotherapy. risk factors for contralateral breast cancer in three different cohorts. Second Cancers Following Retinoblastoma A cohort of 1,850 Retinoblastoma survivors continues to be monitored for the incidence and mortality of all second primary cancers, primarily of the bone, soft tissue, and melanoma in relation to past radiotherapy and chemotherapy. tiology of contralateral breast is probably related to treatment, genetic and lifestyle risk factors. We are exploring the feasibility of studying treatment and modifiable lifestyle risk factors for contralateral breast cancer in three different cohorts. Secondary Cancers of the Brain, Breast, and Thyroid among Childhood Cancer Survivors In a cohort of 14,000 5-year survivors of childhood cancer we performed nested case-control studies of second primary cancers of the breast, thyroid gland, Saliva/Buccal Cellsry gland, bone, soft tissue and skin to evaluate the relationship between radiation and chemotherapy and risk of these cancers. A novel finding was that thyroid cancer risk was related to prior treatment with alkylating agents among patients exposed to radiation less than 20 Gy to the thyroid. Serum Markers of immunity and Risk of Brain Tumors Evidence that a history of allergy and/or autoimmune diseases is associated with a reduced risk of gliomas in adults will be followed up in a case-control study of adult gliomas nested within 7 million U.S. military personnel with pre-diagnostic serum samples. We will quantify the dose-response relationship between risk of gliomas and levels of selected cytokines/growth factors and immune-related disorders in the subjects.